Substance P (SP) is a polypeptide, naturally occurring in various organs, notably in the central and peripheral nervous system and in the gastro-intestinal wall. Its selective distribution in the nervous system, its localization in nerve endings and its neuropharmacological actions strongly suggest that SP acts as a transmittor or modulator in certain neurons, specially in the primry sensory neurons. The following projects are in progress: 1. A detailed mapping of the distribution of SP in mammals with special reference to the nervous structure. For these studies a specific immunofluorescence technique and a radioimmunological assay have been developed. Attempts will be made to establish the origin of SP in nerve fibres and relate SP primary sensory afferents to a specific modality. 2. Studies on the physiological role of SP in the intestinal wall. Radioimmunoactive SP will be determined in the venous effluent from intestinal segments and the intestinal juice in connection to vagal and sympathetic activation, mechanical stimulation and pharmacological induced changes in intestinal motility and blood flow. 3. Studies on the agonist-antagonist activities and duration of actions of SP analogs in vitro. BIBLIOGRAPHIC REFERENCE: T. Hokfelt, J-O. Kellerth, R. Elde, R. Luft, O. Johansson, G. Nilsson, B. Pernow & A. Arimura: Immunohistochemical studies on the distribution of substance P and somatostatin in primary sensory neurons. In: Sensory Functions of the Skin. Ed. Y. Zotterman. Pergamon Press, Oxford and New York, 1976.